Characterization of the human homolog of the IL-4 induced gene-1 (Fig1)

Chavan, Sangeeta S.; Tian, Wenzhi; Hsueh, Kevin; Jawaheer, Damini; Gregersen, Peter K.; Chu, Charles C.

doi:10.1016/s0167-4781(02)00295-6

Cited by 43 publications

(52 citation statements)

References 44 publications

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“…2 An immediate-early IL4-inducible gene called interleukin fourinduced gene 1 (FIG1/IL4I1) has first been described in the mouse 3 and subsequently characterized in human B cells. 4 IL4I1 mRNA expression is restricted to lymphoid tissues, with the highest levels found in lymph nodes and spleen. 4,5 IL4-activated murine B cells express IL4I1 within 2 hours of stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…4 IL4I1 mRNA expression is restricted to lymphoid tissues, with the highest levels found in lymph nodes and spleen. 4,5 IL4-activated murine B cells express IL4I1 within 2 hours of stimulation. We have demonstrated that high levels of expression of this gene are characteristic of primary mediastinal large B-cell lymphoma (PMBL), a specific subtype of diffuse large B-cell lymphoma.…”

Section: Introductionmentioning

confidence: 99%

“…6 Both human and mouse IL4I1 mRNA sequences encode a protein containing a putative signal peptide indicative of potential secretion and a large central domain, highly homologous to flavin-containing amino acid oxidases. 3,4 While sharing high similarity over the majority of the sequence (547 amino acids of the 567 in the human sequence), the human and mouse proteins diverge substantially at their C-terminal region. 4 The IL4I1 protein shares the highest similarity with proteins presenting L-amino acid oxidase (LAAO) activity, such as snake venom LAAO, 7,8 and mouse milk LAAO.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 While sharing high similarity over the majority of the sequence (547 amino acids of the 567 in the human sequence), the human and mouse proteins diverge substantially at their C-terminal region. 4 The IL4I1 protein shares the highest similarity with proteins presenting L-amino acid oxidase (LAAO) activity, such as snake venom LAAO, 7,8 and mouse milk LAAO. 9 Recently, Mason et al have demonstrated that mouse IL4I1 (mIL4I1) possesses an LAAO activity toward aromatic amino acids.…”

Section: Introductionmentioning

confidence: 99%

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Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Boulland

Marquet

Molinier‐Frenkel

et al. 2007

Blood

155

177

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Interleukin-4-induced gene 1 (IL4I1) was first described as a B-cell IL4-inducible gene and is highly expressed in primary mediastinal B-cell lymphomas. We established stable HEK293 clones expressing human and mouse IL4I1 to examine their biochemical properties and function. Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1. We showed that IL4I1 has L-amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine. Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigenpresenting cell/T-lymphocyte cross-talk. Indeed, hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4 ؉ and CD8 ؉ T cells. IntroductionInterleukin-4 (IL4) is the master cytokine for T-helper type 2 (Th2) lymphocyte differentiation and function. Along with its important role in B-lymphocyte stimulation by T-helper cells in germinal centers of secondary lymphoid organs, it also regulates the growth and function of many different cell types of the immune system. 1 IL4 transcriptional effects are primarily mediated by the signalization and transcription factor 6 (STAT6), which is responsible for the induction and repression of multiple target genes. 2 An immediate-early IL4-inducible gene called interleukin fourinduced gene 1 (FIG1/IL4I1) has first been described in the mouse 3 and subsequently characterized in human B cells. 4 IL4I1 mRNA expression is restricted to lymphoid tissues, with the highest levels found in lymph nodes and spleen. 4,5 IL4-activated murine B cells express IL4I1 within 2 hours of stimulation. We have demonstrated that high levels of expression of this gene are characteristic of primary mediastinal large B-cell lymphoma (PMBL), a specific subtype of diffuse large B-cell lymphoma. 5 The high expression of IL4I1 by PMBL may result from the constitutive activation of STAT6 in these tumors. 6 Both human and mouse IL4I1 mRNA sequences encode a protein containing a putative signal peptide indicative of potential secretion and a large central domain, highly homologous to flavin-containing amino acid oxidases. 3,4 While sharing high similarity over the majority of the sequence (547 amino acids of the 567 in the human sequence), the human and mouse proteins diverge substantially at their C-terminal region. 4 The IL4I1 protein shares the highest similarity with proteins presenting L-amino acid oxidase (LAAO) activity, such as snake venom LAAO,7,8 and mouse milk LAAO. 9 Recently, Mason et al have demonstrated that mouse IL4I1 (mIL4I1) possesses an LAAO activity toward aromatic amino acids. The enzyme was mostly active at acidic pH, in contrast to other known members of the LAAO family, and its expression was restricted primarily to lysosomes. 10 In this work, w...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Boulland

Marquet

Molinier‐Frenkel

et al. 2007

Blood

155

177

View full text Add to dashboard Cite

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“…In human, IL4I1 has been assigned to chromosome 19q13.3-19q13.4, a hot spot for susceptibility to several autoimmune diseases (CHAVAN et al 2002). Based on comparative genome data between human and cattle (GOLDAMMER et al 2002), an assignment of IL4I1 to Bos taurus chromosome 18 (BTA18) has been predicted within a quantitative trait locus for somatic cell score (KÜHN et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic and radiation hybrid mapping of the bovine <i>interleukin 4 induced 1 (IL4I1)</i> gene to cattle chromosome 18 (Brief Report)

2009

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Abstract. The interleukin 4 induced 1 (IL4I1) gene, also known as FIG1, encodes a lysosomal protein in B cells with L-amino oxidase (EC 1.4.3.2) property and a high preference for aromatic amino acid substrates implicating a fundamental role in antigene processing and presentation (MANSON et al. 2004). In human, IL4I1 has been assigned to chromosome 19q13.3-19q13.4, a hot spot for susceptibility to several autoimmune diseases (CHAVAN et al. 2002). Based on comparative genome data between human and cattle (GOLDAMMER et al. 2002), an assignment of IL4I1 to Bos taurus chromosome 18 (BTA18) has been predicted within a quantitative trait locus for somatic cell score (KÜHN et al. 2003). This prediction is supported by the putative bovine sequence for IL4I1, LOC520692, which has been assigned to BTA18 close to 56.1 megabases within the annotated bovine sequence (NCBI build Btau-4.0). Therefore, we started positional cloning of bovine IL4I1, as a candidate gene related to adaptive immunity, i.e. during udder infections in cattle. Here we present the physical assignment of the bovine IL4I1 gene by fluorescence in situ hybridization (FISH) and radiation hybrid (RH) mapping.

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Dichotomy between factors inducing the immunosuppressive enzyme IL‐4‐induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes

et al. 2010

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MU and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MU and DC are the major producers of the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by MU and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various proinflammatory stimuli through the activation of the transcription factors NF-jB and/or STAT1. B cells also express IL4I1 in response to NF-jB-activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN-c but respond to stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T-cell proliferation and production of IFN-c and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo.

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Characterization of the human homolog of the IL-4 induced gene-1 (Fig1)

Cited by 43 publications

References 44 publications

Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Cytogenetic and radiation hybrid mapping of the bovine <i>interleukin 4 induced 1 (IL4I1)</i> gene to cattle chromosome 18 (Brief Report)

Dichotomy between factors inducing the immunosuppressive enzyme IL‐4‐induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes

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Characterization of the human homolog of the IL-4 induced gene-1 (Fig1)

Cited by 43 publications

References 44 publications

Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation

Cytogenetic and radiation hybrid mapping of the bovine &lt;i&gt;interleukin 4 induced 1 (IL4I1)&lt;/i&gt; gene to cattle chromosome 18 (Brief Report)

Dichotomy between factors inducing the immunosuppressive enzyme IL‐4‐induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes

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Cytogenetic and radiation hybrid mapping of the bovine <i>interleukin 4 induced 1 (IL4I1)</i> gene to cattle chromosome 18 (Brief Report)